Melatonin synthesis route

Abstract

The invention relates to the technical field of melatonin synthesis, in particular to a melatonin synthesis route. The preparation method comprises the following steps: placing a base material in ammonia water, cooling, filtering, washing and drying to obtain a first material, placing the obtained first material in N, N-dimethylformamide for ultrasonic treatment, adding lithium aluminum hydride for reflux treatment, dissolving with diluted hydrochloric acid, adjusting the pH value, carrying out suction filtration, washing with deionized water, and drying to obtain a second material. And finally, placing the obtained second material in N, N-dimethylformamide for ultrasonic treatment, adding acetic anhydride, adjusting the pH value with a sodium hydroxide solution, cooling, carrying out suction filtration, washing with deionized water, and drying to obtain a finished product, namely melatonin. The melatonin prepared by the preparation method disclosed by the invention not only has better yield, but also has excellent purity, and the quality of the melatonin is effectively ensured.

Description

Technical Field

[0001] The invention relates to the technical field of melatonin synthesis, in particular to a melatonin synthesis route. Background Art

[0002] Melatonin is one of the hormones secreted by the pineal gland in the brain. Melatonin belongs to the class of indole heterocyclic compounds, and its chemical name is N-acetyl-5-methoxytryptamine, also known as pinealogen, melatonin, and melatonin. Melatonin not only has the functions of improving insulin resistance, regulating liver glucose metabolism, regulating skeletal muscle sugar metabolism, regulating fat sugar metabolism, and protecting pancreatic beta cells, but also can scavenge free radicals, regulate cell apoptosis, delay the aging process, regulate sleep and reproductive function, improve the body's immunity, improve cardiovascular and cerebrovascular diseases, and lower blood sugar. Therefore, melatonin has a very broad application prospect in the pharmaceutical, food and other industries.

[0003] In the patent document with application number "CN200910033396.9" and title "A method for preparing melatonin", it is recorded that "the method uses cheap 4-aminobutyric acid as a raw material, and prepares melatonin through steps such as esterification of carboxyl groups, acylation of amino groups, reduction of esters, oxidation of hydroxyl groups, and Fischer indole cyclization. The raw material used in the method for preparing melatonin provided by the present invention is 4-aminobutyric acid, which has a wide source of raw materials and is low in price. The method for preparing melatonin provided by the present invention has a high total yield, simple reaction conditions and reaction process, and avoids the use of expensive indole derivatives as starting materials used in previous literature, thereby providing a new choice for the preparation and production of melatonin."

[0004] Although the above patent documents can prepare melatonin, they cause great environmental pollution. At the same time, the yield and purity are not good, and further improvement is still needed. Based on this, the present invention provides a melatonin synthesis route to solve the above technical problems! Summary of the invention

[0005] The purpose of the present invention is to provide a synthetic route for melatonin, and the prepared melatonin not only has a good yield but also has excellent purity, thereby effectively ensuring its quality.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] The present invention provides a melatonin synthesis route, comprising the following steps:

[0008] S1, placing the base material in ammonia water, and then cooling, filtering, washing, and drying to obtain a first material;

[0009] S2, placing the obtained first material in N,N-dimethylformamide for ultrasonic treatment, adding lithium aluminum hydride for reflux treatment, then dissolving with dilute hydrochloric acid and adjusting the pH value, filtering, washing with deionized water for 2 to 4 times, and drying to obtain the second material;

[0010] S3. The obtained second material is placed in N,N-dimethylformamide for ultrasonic treatment, acetic anhydride is added, and then the pH value is adjusted with sodium hydroxide solution, cooled, filtered, and washed with deionized water for 2 to 4 times. After drying, a finished product, namely melatonin, is obtained.

[0011] The present invention is further configured as follows: in step S1, the preparation process of the base material is as follows:

[0012] 5-Hydroxyindole is placed in anhydrous ethanol at a solid-liquid ratio of 0.22 to 0.32 g / mL to obtain a first solution;

[0013] Then add oxalyl chloride and 20-22% potassium hydroxide aqueous solution, stir for 65-75 minutes at 4-6°C and 120-140 r / min, filter, wash the filter cake with anhydrous ethanol for 2-4 times, and dry to obtain the base material.

[0014] The present invention is further configured as follows: the addition amount of the oxalyl chloride is 0.02-0.08% of the mass of the first solution, and the addition amount of the potassium hydroxide aqueous solution is 0.12-0.22% of the mass of the first solution.

[0015] The present invention is further configured as follows: in the step S1, the following steps are specifically included:

[0016] Place an appropriate amount of base material in ammonia water at a mass ratio of 0.08-0.18:1 and treat at 5-6°C for 60-70 minutes;

[0017] Then the temperature is raised to 20-24° C. and treated for 60-70 minutes, and then the temperature is raised to 40-48° C. and treated for 30-40 minutes. After cooling, the mixture is filtered and the filter cake is washed with deionized water for 2-4 times. After drying, the first material is obtained.

[0018] The present invention is further configured as follows: the temperature is raised to 40-48° C. at a heating rate of 1-2° C. / min.

[0019] The present invention is further configured as follows: in step S2, the following steps are specifically included:

[0020] The first material is placed in N,N-dimethylformamide at a solid-liquid ratio of 0.05-0.15 g / mL and ultrasonically treated for 20-30 min, lithium aluminum hydride is added thereto, and refluxed at 70-80° C. for 24-26 h;

[0021] The product obtained by refluxing is dissolved with dilute hydrochloric acid, and the pH value is adjusted to 2.2-3.2, and allowed to stand for 15-20 minutes, filtered, and washed with deionized water for 2-4 times, and dried to obtain the second material.

[0022] The present invention is further configured as follows: the addition amount of the lithium aluminum hydride is 0.08-0.18% of the mass of the first material.

[0023] The present invention is further configured as follows: in step S3, the following steps are specifically included:

[0024] The second material is placed in N,N-dimethylformamide at a solid-liquid ratio of 0.02 to 0.12 g / mL and ultrasonically treated for 20 to 30 minutes, and then lithium aluminum hydride is added thereto and treated at 20 to 30° C. for 180 to 200 minutes;

[0025] Then adjust the pH value to 7.0-7.2 with sodium hydroxide solution, let it stand for 15-20 minutes, filter it, wash it with deionized water for 2-4 times, and then dry it to obtain the finished product.

[0026] The present invention is further configured as follows: the added amount of the acetic anhydride is 0.11-0.17% of the mass of the second material.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The present invention is to place the base material in ammonia water, and then cool, filter, wash, and dry to obtain a first material, and then place the obtained first material in N, N-dimethylformamide for ultrasonic treatment, add lithium aluminum hydride for reflux treatment, and then dissolve it with dilute hydrochloric acid and adjust the pH value, filter it with suction, and wash it with deionized water, and then dry it to obtain a second material, and finally place the obtained second material in N, N-dimethylformamide for ultrasonic treatment, add acetic anhydride, and then adjust the pH value with sodium hydroxide solution, cool, filter it with suction, and wash it with deionized water, and dry it to obtain a finished product, that is, melatonin. The melatonin prepared by the present invention not only has a good yield, but also has excellent purity, and effectively guarantees its quality. The melatonin synthesis route provided by the present invention has a broader market prospect and is more suitable for promotion. DETAILED DESCRIPTION

[0029] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] Example 1

[0031] This embodiment provides a melatonin synthesis route, comprising the following steps:

[0032] S1. Place the base material in ammonia water, and then cool, filter, wash and dry to obtain a first material.

[0033] The preparation process of the base material is as follows:

[0034] 5-Hydroxyindole is placed in anhydrous ethanol at a solid-liquid ratio of 0.22 g / mL to obtain a first solution;

[0035] Then, oxalyl chloride and a 20% potassium hydroxide aqueous solution were added thereto, and the mixture was stirred at 4°C and 120 r / min for 65 minutes. After suction filtration, the filter cake was washed twice with anhydrous ethanol and dried to obtain a base material.

[0036] Further, the added amount of oxalyl chloride is 0.02% of the mass of the first solution, and the added amount of the aqueous potassium hydroxide is 0.12% of the mass of the first solution.

[0037] In addition, the preparation of the first material specifically includes the following steps:

[0038] Place an appropriate amount of base material in ammonia water at a mass ratio of 0.08:1 and treat at 5°C for 60 minutes;

[0039] Then the temperature was raised to 20°C and treated for 60 minutes, and then the temperature was raised to 40°C and continued to be treated for 30 minutes. After cooling, the mixture was filtered and the filter cake was washed twice with deionized water and dried to obtain the first material.

[0040] The temperature was increased to 40°C at a heating rate of 1°C / min.

[0041] S2. The first material is placed in N,N-dimethylformamide for ultrasonic treatment, lithium aluminum hydride is added for reflux treatment, and then dissolved with dilute hydrochloric acid and the pH value is adjusted. The material is filtered and washed twice with deionized water. After drying, the second material is obtained.

[0042] Specifically, the following steps are included:

[0043] The first material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.05 g / mL and ultrasonically treated for 20 minutes, and then lithium aluminum hydride was added thereto, and refluxed at 70° C. for 24 hours;

[0044] The refluxed product was dissolved with dilute hydrochloric acid, and the pH value was adjusted to 2.2. The product was allowed to stand for 15 minutes, filtered, and washed twice with deionized water. After drying, a second material was obtained.

[0045] Furthermore, the amount of lithium aluminum hydride added is 0.08% of the mass of the first material.

[0046] S3. The obtained second material is placed in N,N-dimethylformamide for ultrasonic treatment, acetic anhydride is added, and then the pH value is adjusted with sodium hydroxide solution, cooled, filtered, and washed twice with deionized water. After drying, a finished product, namely melatonin, is obtained.

[0047] Specifically, the following steps are included:

[0048] The second material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.02 g / mL and ultrasonically treated for 20 min, and then lithium aluminum hydride was added thereto and treated at 20° C. for 180 min;

[0049] Then, the pH value was adjusted to 7.0 with sodium hydroxide solution, allowed to stand for 15 minutes, filtered, and washed twice with deionized water. After drying, the finished product was obtained.

[0050] Furthermore, the amount of acetic anhydride added is 0.11% of the mass of the second material.

[0051] Example 2

[0052] This embodiment provides a melatonin synthesis route, comprising the following steps:

[0053] S1. Place the base material in ammonia water, and then cool, filter, wash and dry to obtain a first material.

[0054] The preparation process of the base material is as follows:

[0055] 5-Hydroxyindole is placed in anhydrous ethanol at a solid-liquid ratio of 0.24 g / mL to obtain a first solution;

[0056] Then, oxalyl chloride and a 21% potassium hydroxide aqueous solution were added thereto, and the mixture was stirred at 5° C. and 122 r / min for 67 min. After suction filtration, the filter cake was washed three times with anhydrous ethanol and dried to obtain a base material.

[0057] Further, the amount of oxalyl chloride added is 0.03% of the mass of the first solution, and the amount of potassium hydroxide aqueous solution added is 0.14% of the mass of the first solution.

[0058] In addition, the preparation of the first material specifically includes the following steps:

[0059] Place an appropriate amount of base material in ammonia water at a mass ratio of 0.1:1 and treat at 6°C for 62 minutes;

[0060] Then the temperature was raised to 21° C. and treated for 62 min, and then the temperature was raised to 42° C. and treated for 32 min. After cooling, the mixture was filtered and the filter cake was washed 3 times with deionized water. After drying, the first material was obtained.

[0061] The temperature was increased to 42°C at a heating rate of 2°C / min.

[0062] S2. The first material is placed in N,N-dimethylformamide for ultrasonic treatment, lithium aluminum hydride is added for reflux treatment, and then dissolved with dilute hydrochloric acid and the pH value is adjusted. The material is filtered and washed with deionized water for 3 times. After drying, the second material is obtained.

[0063] Specifically, the following steps are included:

[0064] The first material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.07 g / mL and ultrasonically treated for 22 minutes, and lithium aluminum hydride was added thereto, and refluxed at 72° C. for 25 hours;

[0065] The refluxed product was dissolved with dilute hydrochloric acid, and the pH value was adjusted to 2.4. The product was allowed to stand for 16 minutes, filtered, and washed with deionized water for 3 times. After drying, a second material was obtained.

[0066] Furthermore, the amount of lithium aluminum hydride added is 0.1% of the mass of the first material.

[0067] S3. The obtained second material is placed in N,N-dimethylformamide for ultrasonic treatment, acetic anhydride is added, and then the pH value is adjusted with sodium hydroxide solution, cooled, filtered, and washed with deionized water for 3 times. After drying, a finished product, namely melatonin, is obtained.

[0068] Specifically, the following steps are included:

[0069] The second material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.04 g / mL and ultrasonically treated for 22 minutes, and then lithium aluminum hydride was added thereto and treated at 22° C. for 185 minutes;

[0070] Then, the pH value was adjusted to 7.1 with sodium hydroxide solution, allowed to stand for 16 minutes, filtered, and washed with deionized water for 2 to 4 times. After drying, the finished product was obtained.

[0071] Furthermore, the amount of acetic anhydride added is 0.12% of the mass of the second material.

[0072] Example 3

[0073] This embodiment provides a melatonin synthesis route, comprising the following steps:

[0074] S1. Place the base material in ammonia water, and then cool, filter, wash and dry to obtain a first material.

[0075] The preparation process of the base material is as follows:

[0076] 5-Hydroxyindole is placed in anhydrous ethanol at a solid-liquid ratio of 0.27 g / mL to obtain a first solution;

[0077] Then, oxalyl chloride and a 21% potassium hydroxide aqueous solution were added thereto, and the mixture was stirred at 5°C and 130 r / min for 70 minutes. After suction filtration, the filter cake was washed three times with anhydrous ethanol and dried to obtain a base material.

[0078] Further, the amount of oxalyl chloride added is 0.06% of the mass of the first solution, and the amount of potassium hydroxide aqueous solution added is 0.17% of the mass of the first solution.

[0079] In addition, the preparation of the first material specifically includes the following steps:

[0080] Place an appropriate amount of base material in ammonia water at a mass ratio of 0.13:1 and treat at 6°C for 65 minutes;

[0081] Then the temperature was raised to 22° C. and treated for 65 min, and then the temperature was raised to 44° C. and treated for 35 min. After cooling, the mixture was filtered and the filter cake was washed three times with deionized water. After drying, the first material was obtained.

[0082] The temperature was increased to 44°C at a heating rate of 2°C / min.

[0083] S2. The first material is placed in N,N-dimethylformamide for ultrasonic treatment, lithium aluminum hydride is added for reflux treatment, and then dissolved with dilute hydrochloric acid and the pH value is adjusted. The material is filtered and washed with deionized water for 3 times. After drying, the second material is obtained.

[0084] Specifically, the following steps are included:

[0085] The first material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.1 g / mL and ultrasonically treated for 25 min, and then lithium aluminum hydride was added thereto, and refluxed at 75° C. for 25 h;

[0086] The refluxed product was dissolved with dilute hydrochloric acid, and the pH value was adjusted to 2.7. The product was allowed to stand for 17 minutes, filtered, and washed with deionized water for 3 times. After drying, the second material was obtained.

[0087] Furthermore, the amount of lithium aluminum hydride added is 0.1% of the mass of the first material.

[0088] S3. The obtained second material is placed in N,N-dimethylformamide for ultrasonic treatment, acetic anhydride is added, and then the pH value is adjusted with sodium hydroxide solution, cooled, filtered, and washed with deionized water for 3 times. After drying, a finished product, namely melatonin, is obtained.

[0089] Specifically, the following steps are included:

[0090] The second material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.07 g / mL and ultrasonically treated for 25 min, and then lithium aluminum hydride was added thereto and treated at 25° C. for 190 min;

[0091] Then, the pH value was adjusted to 7.1 with sodium hydroxide solution, allowed to stand for 17 minutes, filtered, and washed three times with deionized water. After drying, the finished product was obtained.

[0092] Furthermore, the amount of acetic anhydride added is 0.14% of the mass of the second material.

[0093] Example 4

[0094] This embodiment provides a melatonin synthesis route, comprising the following steps:

[0095] S1. Place the base material in ammonia water, and then cool, filter, wash and dry to obtain a first material.

[0096] The preparation process of the base material is as follows:

[0097] 5-Hydroxyindole is placed in anhydrous ethanol at a solid-liquid ratio of 0.31 g / mL to obtain a first solution;

[0098] Then, oxalyl chloride and a 21% potassium hydroxide aqueous solution were added thereto, and the mixture was stirred at 6° C. and 135 r / min for 72 minutes. After suction filtration, the filter cake was washed three times with anhydrous ethanol and dried to obtain a base material.

[0099] Further, the amount of oxalyl chloride added is 0.07% of the mass of the first solution, and the amount of potassium hydroxide aqueous solution added is 0.2% of the mass of the first solution.

[0100] In addition, the preparation of the first material specifically includes the following steps:

[0101] Place an appropriate amount of base material in ammonia water at a mass ratio of 0.16:1 and treat at 6°C for 68 minutes;

[0102] Then the temperature was raised to 23°C and treated for 68 minutes, and then the temperature was raised to 47°C and treated for 38 minutes. After cooling, the mixture was filtered and the filter cake was washed three times with deionized water. After drying, the first material was obtained.

[0103] The temperature was increased to 47°C at a heating rate of 2°C / min.

[0104] S2. The first material is placed in N,N-dimethylformamide for ultrasonic treatment, lithium aluminum hydride is added for reflux treatment, and then dissolved with dilute hydrochloric acid and the pH value is adjusted. The material is filtered and washed with deionized water for 3 times. After drying, the second material is obtained.

[0105] Specifically, the following steps are included:

[0106] The first material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.14 g / mL and ultrasonically treated for 28 minutes, and lithium aluminum hydride was added thereto, and refluxed at 78° C. for 25 hours;

[0107] The refluxed product was dissolved with dilute hydrochloric acid, and the pH value was adjusted to 3.1. The product was allowed to stand for 19 minutes, filtered, and washed with deionized water for 3 times. After drying, the second material was obtained.

[0108] Furthermore, the amount of lithium aluminum hydride added is 0.17% of the mass of the first material.

[0109] S3. The obtained second material is placed in N,N-dimethylformamide for ultrasonic treatment, acetic anhydride is added, and then the pH value is adjusted with sodium hydroxide solution, cooled, filtered, and washed with deionized water for 3 times. After drying, a finished product, namely melatonin, is obtained.

[0110] Specifically, the following steps are included:

[0111] The second material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.11 g / mL and ultrasonically treated for 28 minutes, and then lithium aluminum hydride was added thereto and treated at 28° C. for 195 minutes;

[0112] Then, the pH value was adjusted to 7.1 with sodium hydroxide solution, allowed to stand for 19 minutes, filtered, and washed three times with deionized water. After drying, the finished product was obtained.

[0113] Furthermore, the amount of acetic anhydride added is 0.16% of the mass of the second material.

[0114] Example 5

[0115] This embodiment provides a melatonin synthesis route, comprising the following steps:

[0116] S1. Place the base material in ammonia water, and then cool, filter, wash and dry to obtain a first material.

[0117] The preparation process of the base material is as follows:

[0118] 5-Hydroxyindole is placed in anhydrous ethanol at a solid-liquid ratio of 0.32 g / mL to obtain a first solution;

[0119] Then, oxalyl chloride and a 22% potassium hydroxide aqueous solution were added thereto, and the mixture was stirred at 6° C. and 140 r / min for 75 min. After suction filtration, the filter cake was washed four times with anhydrous ethanol and dried to obtain a base material.

[0120] Further, the amount of oxalyl chloride added is 0.08% of the mass of the first solution, and the amount of potassium hydroxide aqueous solution added is 0.22% of the mass of the first solution.

[0121] In addition, the preparation of the first material specifically includes the following steps:

[0122] Place an appropriate amount of base material in ammonia water at a mass ratio of 0.18:1 and treat at 6°C for 70 minutes;

[0123] Then the temperature was raised to 24°C and treated for 70 minutes, and then the temperature was raised to 48°C and continued to be treated for 30-40 minutes. After cooling, the mixture was filtered and the filter cake was washed 4 times with deionized water. After drying, the first material was obtained.

[0124] The temperature was increased to 48°C at a heating rate of 2°C / min.

[0125] S2. The first material is placed in N,N-dimethylformamide for ultrasonic treatment, lithium aluminum hydride is added for reflux treatment, and then dissolved with dilute hydrochloric acid and the pH value is adjusted. The material is filtered and washed with deionized water for 4 times. After drying, the second material is obtained.

[0126] Specifically, the following steps are included:

[0127] The first material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.15 g / mL and ultrasonically treated for 30 min, and then lithium aluminum hydride was added thereto, and refluxed at 80° C. for 26 h;

[0128] The refluxed product was dissolved with dilute hydrochloric acid, and the pH value was adjusted to 3.2. The product was allowed to stand for 20 minutes, filtered, and washed with deionized water for 4 times. After drying, a second material was obtained.

[0129] Furthermore, the amount of lithium aluminum hydride added is 0.18% of the mass of the first material.

[0130] S3. The obtained second material is placed in N,N-dimethylformamide for ultrasonic treatment, acetic anhydride is added, and then the pH value is adjusted with sodium hydroxide solution, cooled, filtered, and washed with deionized water for 4 times. After drying, a finished product, namely melatonin, is obtained.

[0131] Specifically, the following steps are included:

[0132] The second material was placed in N,N-dimethylformamide at a solid-liquid ratio of 0.12 g / mL and ultrasonically treated for 30 min, and then lithium aluminum hydride was added thereto and treated at 30° C. for 200 min;

[0133] Then, the pH value was adjusted to 7.2 with sodium hydroxide solution, allowed to stand for 20 minutes, filtered, and washed 4 times with deionized water. After drying, the finished product was obtained.

[0134] Furthermore, the amount of acetic anhydride added is 0.17% of the mass of the second material.

[0135] Performance test: The melatonin samples provided in Examples 1 to 5 are respectively marked as Examples 1 to 5; and the relevant properties of the melatonin provided in Examples 1 to 5 are respectively tested as follows:

[0136] Table 1 Yield test results of each group

[0137] Group Yield (%) Example 1 Group 85.6 Example 2 Group 85.8 Example 3 Group 85.2 Example 4 group 85.4 Example 5 group 85.2

[0138] Table 2 Purity test results of each group

[0139] Group purity(%) Example 1 Group 95.4 Example 2 Group 95.1 Example 3 Group 95.6 Example 4 group 95.2 Example 5 group 95.2

[0140] By comparing and analyzing the relevant data in Table 1 and Table 2, it can be seen that the melatonin prepared by the present invention not only has a good yield, but also has excellent purity, effectively ensuring its quality and quality. This shows that the melatonin synthesis route provided by the present invention has a broader market prospect and is more suitable for promotion.

[0141] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0142] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific implementation methods described. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A melatonin synthesis route, characterized in that: The following steps are involved: S1, placing the base material in ammonia water, and then cooling, filtering, washing, and drying to obtain a first material; S2, placing the obtained first material in N,N-dimethylformamide for ultrasonic treatment, adding lithium aluminum hydride for reflux treatment, then dissolving with dilute hydrochloric acid and adjusting the pH value, filtering, washing with deionized water for 2 to 4 times, and drying to obtain the second material; S3. The obtained second material is placed in N,N-dimethylformamide for ultrasonic treatment, acetic anhydride is added, and then the pH value is adjusted with sodium hydroxide solution, cooled, filtered, and washed with deionized water for 2 to 4 times. After drying, a finished product, namely melatonin, is obtained.

2. A melatonin synthesis route according to claim 1, characterized in that: In step S1, the preparation process of the base material is as follows: 5-Hydroxyindole is placed in anhydrous ethanol at a solid-liquid ratio of 0.22 to 0.32 g / mL to obtain a first solution; Then add oxalyl chloride and 20-22% potassium hydroxide aqueous solution, stir for 65-75 minutes at 4-6°C and 120-140 r / min, filter, wash the filter cake with anhydrous ethanol for 2-4 times, and dry to obtain the base material.

3. A melatonin synthesis route according to claim 2, characterized in that: The added amount of the oxalyl chloride is 0.02-0.08% of the mass of the first solution, and the added amount of the potassium hydroxide aqueous solution is 0.12-0.22% of the mass of the first solution.

4. A melatonin synthesis route according to claim 1, characterized in that: In the step S1, the following steps are specifically included: Place an appropriate amount of base material in ammonia water at a mass ratio of 0.08-0.18:1 and treat at 5-6°C for 60-70 minutes; Then the temperature is raised to 20-24° C. and treated for 60-70 minutes, and then the temperature is raised to 40-48° C. and treated for 30-40 minutes. After cooling, the mixture is filtered and the filter cake is washed with deionized water for 2-4 times. After drying, the first material is obtained.

5. A melatonin synthesis route according to claim 4, characterized in that: The temperature was raised to 40-48°C at a heating rate of 1-2°C / min.

6. A melatonin synthesis route according to claim 1, characterized in that: In the step S2, the following steps are specifically included: The first material is placed in N,N-dimethylformamide at a solid-liquid ratio of 0.05-0.15 g / mL and ultrasonically treated for 20-30 min, lithium aluminum hydride is added thereto, and refluxed at 70-80° C. for 24-26 h; The product obtained by refluxing is dissolved with dilute hydrochloric acid, and the pH value is adjusted to 2.2-3.2, and allowed to stand for 15-20 minutes, filtered, and washed with deionized water for 2-4 times, and dried to obtain the second material.

7. A melatonin synthesis route according to claim 6, characterized in that: The added amount of lithium aluminum hydride is 0.08-0.18% of the mass of the first material.

8. A melatonin synthesis route according to claim 1, characterized in that: In the step S3, the following steps are specifically included: The second material is placed in N,N-dimethylformamide at a solid-liquid ratio of 0.02 to 0.12 g / mL and ultrasonically treated for 20 to 30 minutes, and then lithium aluminum hydride is added thereto and treated at 20 to 30° C. for 180 to 200 minutes; Then adjust the pH value to 7.0-7.2 with sodium hydroxide solution, let it stand for 15-20 minutes, filter it, wash it with deionized water for 2-4 times, and then dry it to obtain the finished product.

9. A melatonin synthesis route according to claim 8, characterized in that: The added amount of acetic anhydride is 0.11-0.17% of the mass of the second material.